2016 ᖺ 1 ᭶ 25 ᪥║่⃭ᛶヨ㦂௦᭰ἲࡢホ౯ሗ࿌᭩෌ᵓ⠏ࣄࢺゅ⭷ᵝୖ⓶ࣔࢹࣝἲ(Reconstructed Human Cornea-like Epithelium Test Method: RhCE ἲ)║่⃭ᛶ௦᭰ἲ㈨ᩱ⦅⧩ጤဨ఍

ᖹᡂ 28 ᖺ㸦2016 ᖺ㸧1 ᭶ 25 ᪥172016 ᖺ 1 ᭶ 25 ᪥║่⃭ᛶ௦᭰ἲ㈨ᩱ⦅⧩ጤဨ఍ᑠᆏ ᛅྖ  㸦୍⯡㈈ᅋἲே ṧ␃㎰⸆◊✲ᡤ㸧బࠎᮌ ṇ἞ 㸦࢔ࢵࣦ࢕ྜྠ఍♫㸧➉ෆ ᑠⱑ  㸦P&G ࢖ࣀ࣮࣋ࢩࣙࣥྜྠ఍♫㸧᳃ᮧ ᬛ⨾ 㸦୍⯡㈈ᅋἲே 㣗ရ⸆ရᏳ඲ࢭࣥࢱ࣮ ⛙㔝◊✲ᡤ㸧ྜྷᮧ ຌ  㸦ᮾி⌮⛉኱Ꮫྡ㄃ᩍᤵ㸧

282016 ᖺ 1 ᭶ 25 ᪥␎ㄒ
CAS: Chemical Abstracts Services
CE: Cosmetics EuropeEURL ECVAM: the European Union Reference Laboratory for Alternatives to Animal Testing
ESAC: ECVAM Scientific Advisory Committee
GHS: Globally Harmonized System of Classification and Labeling of Chemicals
JaCVAM: Japanese Center for the Validation of Alternative Methods
MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
OD: optical density
OECD: Organization for Economic Co-operation and Development
SOP: Standard Operating Procedures
TG: Test Guideline
UN: United Nations

392016 ᖺ 1 ᭶ 25 ᪥せ᪨෌ᵓ⠏ࣄࢺゅ⭷ᵝୖ⓶ࣔࢹࣝἲ㸦Reconstructed Human Cornea-like Epithelium Test Method㸸RhCEἲ㸧ࡣࠊ໬Ꮫ≀㉁ࡢ RhCE ⤌⧊࡟ᑐࡍࡿ⣽⬊ẘᛶࢆᣦᶆ࡟⏝࠸ࠊࡑࡢ≀㉁ࡢ║่⃭ᛶࢆホ౯ࡍࡿヨ㦂ἲ࡛࠶ࡿࠋUN GHS ༊ศእ≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚ EURL ECVAM ࡜ CE ࡢඹྠࣂࣜࢹ࣮ࢩࣙࣥࢆ⤒࡚ 2015 ᖺ࡟ OECD ࡟ࡼࡾࢸࢫࢺ࢞࢖ࢻࣛ࢖ࣥ TG 492 ࡜ࡋ࡚᥇ᢥࡉࢀࡓࠋJaCVAM ║่⃭ᛶ௦᭰ἲ㈨ᩱ⦅⧩ጤဨ఍ࡣࠊTG 492 ࡛♧ࡉࢀࡓ RhCE ἲࡢ 1 ࡘ࡛࠶ࡿ EpiOcularTM ࢆ⏝࠸ࡓ║่⃭ᛶヨ㦂࡟ࡘ࠸࡚ࠊࣂࣜࢹ࣮ࢩࣙࣥሗ࿌᭩ࠊ➨୕⪅ホ౯ሗ࿌᭩ࠊ㛵㐃ㄽᩥ࡞࡝ࢆࡶ࡜࡟ヨ㦂ἲࡢᴫせ࠾ࡼࡧጤဨ఍ࡢពぢࢆࡲ࡜ࡵࡓࠋ ᚑ᮶ࡢ࢘ࢧࢠࢆ⏝࠸ࡓ Draize ἲࡢ⤖ᯝࢆᇶ‽࡜ࡋ࡚ṇ☜ࢆホ౯ࡋࡓ࡜ࡁࠊ୍⮴ᗘࡣ 79.7%ࠊഇ㝧ᛶ⋡ࡣ 37.0%ࠊഇ㝜ᛶ⋡ࡣ 4.3%࡛࠶ࡗࡓࠋᢏ⾡⛣㌿ᛶ࡟㛵ࡋ࡚ᠱᛕࡉࢀࡿ⤖ᯝࡣᚓࡽࢀ࡚࠾ࡽࡎࠊ᪋タෆ෌⌧ᛶ࠾ࡼࡧ᪋タ㛫෌⌧ᛶࡣ࡝ࡕࡽࡶ 90%௨ୖ࡛࠶ࡗࡓࠋࡇࢀࡽࡢ್ࡣࠊࣂࣜࢹ࣮ࢩࣙࣥ㐠Ⴀጤဨ఍ࡀᐃࡵࡓᇶ‽ࢆ‶ࡓࡋ࡚࠸ࡓࠋ ᮏጤဨ఍ࡣࠊRhCE ἲࡣ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡛ UN GHS ༊ศእ≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚⏝࠸ࡿࡇ࡜ࡀ࡛ࡁࡿ࡜⤖ㄽࡋࡓࠋ410

2016 ᖺ 1 ᭶ 25 ᪥1. ࡲ࠼࠾ࡁ໬Ꮫ≀㉁ࡢ║่⃭ᛶࢆホ౯ࡍࡿ᪉ἲ࡜ࡋ࡚ᚑ᮶౑⏝ࡉࢀ࡚ࡁࡓࡢࡣࠊDraize ἲ࡜࠸࠺࢘ࢧࢠࢆ⏝࠸ࡓື≀ヨ㦂࡛࠶ࡿࠋࡋ࠿ࡋࠊ㏆ᖺࡢື≀⚟♴࡟ᑐࡍࡿ㛵ᚰࡢ㧗ࡲࡾࡸḢᕞ࡟࠾ࡅࡿἲつไᨵṇࡣࠊࡑࡢ௦᭰ἲࡢ㛤Ⓨ࣭ࣂࣜࢹ࣮ࢩࣙࣥࢆಁ㐍ࡋࡓࠋOECD ࡀࢸࢫࢺ࢞࢖ࢻࣛ࢖ࣥ࡜ࡋ࡚ࡍ࡛࡟᥇ᢥࡋࡓ௦
᭰ἲࡣࠊ࢘ࢩ᦬ฟゅ⭷ࡢΰ⃮࠾ࡼࡧ㏱㐣ᛶヨ㦂ἲ㸦BCOP ἲࠊTG 437㸧ࠊࢽ࣡ࢺࣜ᦬ฟ║⌫ࢆ⏝࠸ࡓ║่⃭ᛶヨ㦂ἲ㸦ICE ἲࠊTG 438㸧ࠊ࠾ࡼࡧࣇࣝ࢜ࣞࢭ࢖ࣥ₃ฟヨ㦂ἲ㸦FL ἲࠊTG 460㸧ࡢ 3 ヨ㦂ἲ࡛࠶ࡿࠋBCOP ἲ࡜ ICE ἲࡣ㣗⏝࡞࡝ࡢ┠ⓗ࡛ฎศࡉࢀࡓື≀ࡼࡾ᦬ฟࡋࡓჾᐁ࣭⤌⧊ࢆ⏝࠸࡚໬Ꮫ≀㉁ࡢ᭚㟢࡟ࡼࡾ⏕ࡌࡿゅ⭷ࡢ≀⌮ⓗ≉ᛶࡢኚ໬ࢆᣦᶆ࡟║่⃭ᛶࢆホ౯ࡍࡿヨ㦂ἲ࡛ࠊࢺࢵࣉࢲ࢘ࣥ
᪉ᘧ࡟࠾࠸࡚㔜⠜࡞║ࡢയᐖࢆ㉳ࡇࡍ㸦ࡍ࡞ࢃࡕࠊUN GHS ༊ศ 1㸧≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚ࠊࡲ
ࡓ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡟࠾࠸࡚║࡟ᑐࡍࡿ㔜⠜࡞ᦆയᛶࢆ᭷ࡍࡿ≀㉁࠾ࡼࡧ║่⃭ᛶ≀㉁࡜ࡣศ㢮ࡉࢀ࡞࠸㸦ࡍ࡞ࢃࡕࠊUN GHS ༊ศእ㸧≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚⏝࠸ࡽࢀࡿࠋFL ἲࡣᒀ⣽⟶ୖ⓶⣽⬊ࡢ༢ᒙᇵ㣴ࢆ⏝࠸࡚໬Ꮫ≀㉁ࡢ᭚㟢࡟ࡼࡾ⏕ࡌࡿ⣽⬊㛫⤖ྜࡢയᐖࢆᣦᶆ࡟║่⃭ᛶࢆホ౯ࡍࡿヨ㦂ἲ࡛ࠊࢺࢵࣉࢲ࢘ࣥ᪉ᘧ࡛ࡢࡳ⏝࠸ࡽࢀࡿࠋ෌ᵓ⠏ࣄࢺゅ⭷ᵝୖ⓶ࣔࢹࣝἲ㸦Reconstructed Human Cornea-like Epithelium Test Methodࠊ௨ୗ RhCEἲ㸧ࡣࠊ⿕㦂≀㉁ࡢࣄࢺゅ⭷ᵝୖ⓶ࣔࢹࣝ㸦RhCE㸧⤌⧊࡟ᑐࡍࡿ⣽⬊ẘᛶࢆᣦᶆ࡟⏝࠸ࠊࡑࡢ≀㉁ࡢ
║่⃭ᛶࢆホ౯ࡍࡿヨ㦂ἲ࡛࠶ࡿࠋRhCE ⤌⧊࡟⿕㦂≀㉁ࢆ᭚㟢ࡋࡓᚋࠊ㝜ᛶᑐ↷࡜ࡢẚ㍑࡟ࡼࡾ⣽⬊⏕Ꮡ⋡ࢆ⟬ฟࡋ⿕㦂≀㉁ࡢ║่⃭ᛶࢆホ౯ࡍࡿࠋ
RhCE ἲࡣ EURL ECVAM ࡜ CE ࡢඹྠࣂࣜࢹ࣮ࢩࣙࣥ◊✲㸦EURL ECVAM-CE, 2014㸧࠾ࡼࡧ ESACࡢ➨୕⪅ホ౯㸦ESAC, 2014㸧ࢆ⤒࡚ࠊUN GHS ༊ศእ≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚ 2015 ᖺ 7 ᭶࡟ OECD࡟ࡼࡾࢸࢫࢺ࢞࢖ࢻࣛ࢖ࣥ࡟᥇ᢥࡉࢀࡓ㸦TG 492㸧ࠋᮏሗ࿌᭩ࡣࣂࣜࢹ࣮ࢩࣙࣥሗ࿌᭩ࠊ➨୕⪅ホ౯ሗ࿌᭩ࠊ㛵㐃ㄽᩥ࡞࡝ࢆࡶ࡜࡟ OECD TG 492 RhCEἲࡢᴫせࢆㄝ᫂ࡋࠊᮏጤဨ఍ࡢពぢࢆࡲ࡜ࡵࡓࡶࡢ࡛࠶ࡿࠋ2㸬ヨ㦂ἲࡢ఩⨨࡙ࡅ
RhCE ἲࡣࠊUN GHS ༊ศእ≀㉁㸦༢୍≀㉁࠾ࡼࡧΰྜ≀㸧ࢆ᳨ฟࡍࡿࡓࡵ࡟⏝࠸ࡿヨ㦂ἲ࡛࠶ࡿࠋ
3㸬ヨ㦂ἲࡢཎ⌮║่⃭ᛶࡣࠊ≀㉁ࡀゅ⭷ࢆྵࡴ║⾲㠃࡟᥋ゐࡋ⣽⬊യᐖࢆᘬࡁ㉳ࡇࡍࡇ࡜࠿ࡽጞࡲࡿࠋࡑࡢᶵᗎࡣ
ᵝࠎ࡛࠶ࡿࡀࠊ⣽⬊ẘᛶࡀ㔜せ࡞ᙺ๭ࢆᢸࡗ࡚࠸ࡿࠋࡲࡓࠊ≀㉁ࡢ║่⃭ᛶࡣ୺࡟ゅ⭷ࡢึᮇയᐖࡢ
῝ᗘ࡟ࡼࡾỴᐃࡉࢀࠊࡑࢀࡣ⣽⬊Ṛࡢ⛬ᗘ࡜┦㛵㛵ಀ࡟࠶ࡿࠋRhCE ἲࡣࠊ෌ᵓ⠏ࣄࢺゅ⭷ᵝୖ⓶ࣔࢹ࡛ࣝ࠶ࡿ RhCE ⤌⧊ࢆ⏝࠸࡚ࠊ⿕㦂≀㉁ࡢ⣽⬊ẘᛶࢆᣦᶆ࡜ࡋ࡚║่⃭ᛶࢆホ౯ࡍࡿヨ㦂ἲ࡛࠶ࡿࠋ
TG 492 ࡛ㄆࡵࡽࢀ࡚࠸ࡿ RhCE ἲࡣࠊࣄࢺ᪂⏕ඣໟ⓶⣽⬊⏤᮶ࡢᕷ㈍ࡢ RhCE ⤌⧊࡛࠶ࡿࠋ⿕㦂≀㉁ࡀᾮయ
EpiOcularTM ࢆ⏝࠸ࡓ║่⃭ᛶヨ㦂㸦EpiOcularTM EIT㸧࡛࠶ࡿ㸦Kaluzhny et al, 2011㸧ࡢሙྜࡣ⣙ 30 ศ㛫ࠊᅛయࡢሙྜࡣ⣙ 6 ᫬㛫ࠊRhCE ⤌⧊࡟᭚㟢ࡋࡓᚋ࡛ࡢ MTT ࡢྲྀࡾ㎸ࡳ㔞ࢆࡶ࡜࡟ࡋࡓ⣽⬊⏕Ꮡ⋡ࢆ࢚ࣥࢻ࣏࢖ࣥࢺ࡟⏝࠸ࡿࠋࡇࢀࡣࠊMTT ࡀ⬺Ỉ⣲㓝⣲ࡢᇶ㉁࡜࡞ࡿᛶ㉁ࢆ฼⏝ࡋࠊ⣽⬊ෆ࡟ྲྀࡾ㎸ࡲࢀࡓ MTT ࡀ࣑ࢺࢥࣥࢻࣜ࢔ෆ⬺Ỉ⣲㓝⣲࡟ࡼࡾ㑏ඖࡉࢀࠊ⏕ᡂࡉࢀࡓ࣐࣍ࣝ
511

2016 ᖺ 1 ᭶ 25 ᪥ࢨࣥ㔞㸦㟷Ⰽ㸧ࡀ⏕Ꮡ⣽⬊ᩘ࡟ẚ౛ࡍࡿࡇ࡜ࢆᇶᮏཎ⌮࡜ࡋ࡚࠸ࡿ㸦MTT 㑏ඖἲ㸧ࠋ⣽⬊⏕Ꮡ⋡ࡀ㝜ᛶᑐ↷࡜ẚ㍑ࡋ࡚ 60%ࢆ㉸࠼ࡿሙྜࠊ⿕㦂≀㉁ࡣ UN GHS ศ㢮࡟࠾࠸࡚༊ศእ࡛࠶ࡿ࡜ุᐃࡍࡿࠋ
4㸬ヨ㦂ᡭ㡰 ௨ୗ࡟♧ࡍᡭ㡰ࡣࠊTG 492 ࡛ㄆࡵࡽࢀ࡚࠸ࡿ EpiOcularTM EIT ࡟ࡘ࠸࡚ࡢࡶࡢ࡛࠶ࡿࠋEpiOcularTMࡣ࢔࣓ࣜ࢝ࡢ〇㐀ඖࡼࡾ㉎ධ࡛ࡁࡿࠋヲ⣽ࡣࠊTG 492 ࠾ࡼࡧ SOP㸦SOP Version 9, 2015㸧ࢆཧ↷ࡍࡿࡇ࡜ࠋ
4-1. RhCE ⤌⧊ࡢᶵ⬟ⓗ᮲௳ RhCE ⤌⧊ࡢᶵ⬟ⓗ᮲௳࡟ࡣࠊRhCE ⤌⧊ࡢ⏕Ꮡ⋡࡜ࣂࣜ࢔ᶵ⬟ࡀྵࡲࢀࠊࡑࡢチᐜ⠊ᅖࡣ௨ୗࡢ
࡜࠾ࡾ࡛࠶ࡿࠋ
⏕Ꮡ⋡㸸㝜ᛶᑐ↷࡟࠾࠸࡚ 0.8 < OD < 2.5ࣂࣜ࢔ᶵ⬟㸸0.3% Triton X-100 ࡟ᑐࡋ 12.2  ET50 (min)  37.5
㸦ET50㸸⣽⬊⏕Ꮡ⋡ࢆ 50%పୗࡉࡏࡿࡢ࡟ᚲせ࡞᭚㟢᫬㛫㸧ࡇࢀࡽࡣ RhCE ⤌⧊ࡢ〇㐀⪅ࡢฟⲴᇶ‽࡜ࡋ࡚ࡶ᥇⏝ࡉࢀࡿࠋࡲࡓࠊ〇㐀⪅ࡣ⤌⧊Ꮫⓗ᳨ᰝ࡛ RhCE⤌⧊ࡀࣄࢺࡢゅ⭷ୖ⓶ᵝᵓ㐀ࢆ᭷ࡍࡿࡇ࡜ࢆಖドࡋ࡚࠾ࡃᚲせࡀ࠶ࡿࠋ୍᪉ࠊRhCE ⤌⧊ࡢ౑⏝⪅ࡣヨ㦂࡛ᚓࡽࢀࡓ㝧ᛶ࠾ࡼࡧ㝜ᛶᑐ↷ࡢ⤖ᯝࢆ⫼ᬒࢹ࣮ࢱ࡜ẚ㍑ࡋ࡚ࠊ෌⌧ᛶࢆ☜ㄆࡍࡿᚲせࡀ࠶ࡿࠋ4-2. ⿕㦂≀㉁ࡢ㐺⏝ ≀㉁࠶ࡓࡾᑡ࡞ࡃ࡜ࡶ 2 ⤌⧊ࢆ⏝࠸ࡿࠋ⿕㦂≀㉁ࡣㄪ〇ࡏࡎࠊཎయࡑࡢࡶࡢࢆ⏝࠸ࡿࠋ37ÛC ௨ୗ࡛ࣆ࣌ࢵࢺ࡛ᢅ࠼ࡿࡶࡢࡣᾮయ࡜ࡋ࡚ࠊࡑࢀ௨እࡣᅛయ࡜ࡋ࡚ヨ㦂ࢆ⾜࠺ࠋ≉࡟ࠊ⿕㦂≀㉁ࡀ⢓ᛶࡢ࠶ࡿ≀㉁ࡸᶞ⬡࣭࣡ࢵࢡࢫ࣭ࢤࣝ≧≀㉁ࡢሙྜࡣࠊ37±1ÛC ࡛ 15±1 ศ㛫Ỉᾎ࡛࢖࣮ࣥ࢟ࣗ࣋ࢺࡋ࡚ᾮయ
࠿ᅛయ࠿ࢆุ᩿ࡍࡿࠋRhCE ⤌⧊ࡣࣜࣥ㓟⦆⾪⏕⌮㣗ሷỈ㸦Mg2+/Ca2+ free㸧ࢆ⏝࠸࡚ 30±2 ศ㛫ᶆ‽ᇵ㣴᮲௳1࡛๓ฎ⌮ࡍࡿࠋᾮయ⿕㦂≀㉁ࡢሙྜࠊRhCE ⤌⧊࡟ 50 μL ࢆ㐺⏝ࡋࠊᶆ‽ᇵ㣴᮲௳࡛ 30±2 ศ㛫ᇵ㣴ࡍࡿࠋࡑࡢᚋࠊࣜࣥ㓟⦆⾪⏕⌮㣗ሷỈ࡛༑ศ࡟Ὑίࡋ࡚⿕㦂≀㉁ࢆ㝖ཤࡋࠊ12±2 ศ㛫ᐊ࡛ᇵᆅ࡟ᾐₕᚋࠊ᪂ࡓ࡞ᇵᆅࢆ⏝࠸࡚ᶆ‽ᇵ㣴᮲௳࡛ 120±15 ศ㛫ᇵ㣴ࡍࡿࠋᅛయ⿕㦂≀㉁ࡢሙྜࠊRhCE⤌⧊ࡢ⾲㠃ࢆそ࠺ࡢ࡟༑ศ࡞㔞ࠊ⣙ 50 mg ࢆᆒ୍࡟㐺⏝ࡋࠊᶆ‽ᇵ㣴᮲௳࡛ 6±0.25 ᫬㛫ᇵ㣴ࡍࡿࠋࡑࡢᚋࠊࣜࣥ㓟⦆⾪⏕⌮㣗ሷỈ࡛༑ศ࡟Ὑίࡋ࡚⿕㦂≀㉁ࢆ㝖ཤࡋࠊ25±2 ศ㛫ᐊ࡛ᇵᆅ࡟ᾐₕᚋࠊ᪂ࡓ࡞ᇵᆅࢆ⏝࠸࡚ᶆ‽ᇵ㣴᮲௳࡛ 18±0.25 ᫬㛫ᇵ㣴ࡍࡿࠋ 㝧ᛶᑐ↷࡟ࡣ㓑㓟࣓ࢳࣝ㸦CAS No. 79-20-9㸧ࠊ㝜ᛶᑐ↷࡟ࡣ㉸⣧Ỉࡀ᥎ዡࡉࢀࡿࠋᑐ↷≀㉁ࡢ㐺⏝࣭ᚋฎ⌮ࡣᑐ↷࡜࡞ࡿ⿕㦂≀㉁㸦ᾮయࡲࡓࡣᅛయ㸧ࡢ᮲௳࡟‽ࡌࡿࠋ
4-3. ⣽⬊⏕Ꮡ⋡ࡢ⟬ฟ⣽⬊⏕Ꮡ⋡⟬ฟ࡟ࡣ MTT 㑏ඖἲࢆ⏝࠸ࡿࠋᇵᆅࢆ㝖ཤࡋࠊ1 mg/mL MTT ⁐ᾮ 0.3 mL ୰࡛ 180±10ศ㛫ᶆ‽ᇵ㣴᮲௳࡛཯ᛂࡉࡏࠊࡑࡢᚋ 2 mL ࢖ࢯࣉࣟࣃࣀ࣮ࣝ㸦ࡲࡓࡣྠᵝ࡞⁐፹㸧࡛㟷Ⰽࡢ࣐࣍ࣝࢨࣥࢆᢳฟࡍࡿࠋᾮయ⿕㦂≀㉁ࡢሙྜࡣࠊRhCE ⤌⧊ࡢୖ㒊࣭ᗏ㒊୧᪉࠿ࡽᢳฟࡍࡿࠋᅛయ⿕㦂≀㉁࠾ࡼࡧⰍࡢ௜࠸࡚࠸ࡿᾮయ⿕㦂≀㉁ࡢሙྜࡣࠊ⤌⧊࡟ṧᏑࡍࡿ⿕㦂≀㉁ࡢΰධࢆ᭱ᑠ㝈࡟ᢚ࠼ࡿࡓࡵࠊ
1

ᬯᡤࠊ37s1ÛCࠊ5s1% CO2ࠊ㧗‵ᗘ6122016 ᖺ 1 ᭶ 25 ᪥࣐࣍ࣝࢨࣥࡢᢳฟࡣ RhCE ⤌⧊ࡢᗏ㒊ࡢࡳ࠿ࡽ⾜࠺ࠋᾮయ⿕㦂≀㉁࡛ࡶࠊὙίࡋ࡙ࡽ࠸ሙྜ࡟ࡣࠊᗏ
㒊ࡢࡳ࠿ࡽᢳฟࢆ⾜࠺ࠋྠ᫬ᑐ↷≀㉁࡟ᑐࡋ࡚ࡢᢳฟ᪉ἲࡣ⿕㦂≀㉁࡜ྠࡌ࡜ࡍࡿࠋᢳฟࡋࡓ࣐࣍ࣝ
ࢨࣥࡢᐃ㔞ࡣ OD570nm

ᐃࡲࡓࡣ HPLC/UPLC ࡛⾜࠺ࠋ⿕㦂≀㉁ࡀ MTT 㑏ඖ≀㉁ࡢሙྜࠊ࠶ࡿ࠸ࡣ࣐࣍ࣝࢨࣥ࡜ྠࡌࡼ࠺࡞Ἴ㛗㸦570 nm ㏆㎶㸧࡟྾཰ࢆᣢࡘ╔Ⰽ≀㉁ࡢሙྜࠊ྾ගᗘ⿵ṇࢆ⾜࠺ᚲせࡀ࠶ࡿࠋࡑࡢᡭ㡰࡟ࡘ࠸࡚ࡣ TG ᮏᩥࡢㄝ᫂࠾ࡼࡧ
ANNEX II ࡢࣇ࣮ࣟࢳ࣮ࣕࢺࢆཧ↷ࡍࡿࡇ࡜ࠋ
4-4. ヨ㦂ᡂ❧ࡢᢎㄆᇶ‽௨ୗࡢ᮲௳ࢆ‶ࡓࡋࡓሙྜࠊヨ㦂ࡢᡂ❧ࢆᢎㄆࡍࡿࠋ1㸧㝜ᛶᑐ↷ࡢ OD ࡀ 0.8 < OD < 2.5 ࡛࠶ࡿࡇ࡜ࠋ2㸧㝧ᛶᑐ↷ࡢᖹᆒ⣽⬊⏕Ꮡ⋡ࡀ 50%ᮍ‶࡛࠶ࡿࡇ࡜ࠋ3㸧⿕㦂≀㉁࠾ࡼࡧ㝜ᛶ࣭㝧ᛶᑐ↷ࡢࡑࢀࡒࢀ࡟࠾࠸࡚ࠊ2 ⤌⧊ࢆ⏝࠸ࡓሙྜࡣ⣽⬊⏕Ꮡ⋡ࡢᕪࡀ
20%ᮍ‶ࠊ3 ⤌⧊௨ୖࢆ⏝࠸ࡓሙྜࡣ⣽⬊⏕Ꮡ⋡ࡢᶆ‽೫ᕪࡀ 18%௨ୗ࡛࠶ࡿࡇ࡜ࠋ
4-5. ่⃭ᛶࡢุᐃ่⃭ᛶุᐃࡢ࢝ࢵࢺ࢜ࣇ್ࡣᖹᆒ⣽⬊⏕Ꮡ⋡ 60%࡛࠶ࡿࠋࡍ࡞ࢃࡕࠊᖹᆒ⣽⬊⏕Ꮡ⋡ࡀ 60%ࢆ㉸࠼ࡓሙྜࠊ⿕㦂≀㉁ࡣ GHS ༊ศእ࡜ุ᩿ࡉࢀࡿࠋᖹᆒ⣽⬊⏕Ꮡ⋡ࡀ 60%௨ୗࡢሙྜࠊᮏヨ㦂ἲ࡛ࡣഇ㝧ᛶࡀ⏕ࡌ࠼ࡿࡋࠊࡲࡓ༊ศ 1 ࡜༊ศ 2 ࢆ᳨ฟ࡛ࡁ࡞࠸ࡇ࡜࠿ࡽࠊ௚ࡢヨ㦂ἲ࡟ࡼࡿ㏣ຍヨ㦂ࡀᚲせ࡜࡞ࡿࠋ5㸬ࣂࣜࢹ࣮ࢩࣙࣥヨ㦂 EURL ECVAM ࡜ CE ࡢ༠ྠ࡛ EpiOcularTM EIT ࡢࣂࣜࢹ࣮ࢩࣙࣥヨ㦂ࡀ⾜ࢃࢀࡓࠋṇ☜ᛶࡢホ౯ࡢࡓࡵ࡟ᚲせ࡞ື≀ヨ㦂ࡢࢹ࣮ࢱࢆᣢࡗ࡚࠸ࡿࡇ࡜ࢆ๓ᥦ᮲௳࡟ࠊUN GHS ༊ศ≀㉁࣭༊ศእ≀㉁ࡸᅛ
య࣭ᾮయ➼ࡢࣂࣛࣥࢫࢆ⪃៖ࡋ࡚⿕㦂≀㉁ࡢ㑅ᢥࡀ⾜ࢃࢀࡓ㸦Appendix 1㸧ࠋ ࢥ࣮ࢻ໬ࡉࢀࡓ 107 ≀㉁࡟ࡘ࠸࡚ࡍ࡭࡚ࢆ 3 ᪋タ࡛ヨ㦂ࡋࡓ㸦ᮏヨ㦂㸧ࠋヨ㦂ࡣࡍ࡭࡚ࡢ⿕㦂≀㉁࡟ࡘ࠸࡚ 3 ᅇᐇ᪋ࡉࢀࡓࠋᅛయ≀㉁࡟ᑐࡋ࡚ࡣࠊࡑࡢᚋࣉࣟࢺࢥ࣮ࣝࡢ᭱㐺໬㸦⿕㦂≀㉁ࡢ᭚㟢᫬㛫ࢆ 90±5 ศ࠿ࡽ 6±0.25 ᫬㛫࡟ኚ᭦㸧ࡀ⾜ࢃࢀࡓࡓࡵࠊ107 ≀㉁୰ࡢᅛయ࠾ࡼࡧ᪂ࡓ࡞ᅛయ 8 ≀㉁࡟ࡘ࠸࡚ࠊ㏣ຍヨ㦂ࡀ 1 ᪋タ࡛⾜ࢃࢀࡓࠋࡇࡢࣂࣜࢹ࣮ࢩࣙࣥヨ㦂࡛ࡣ྾ගᗘ࡛࣐࣍ࣝࢨࣥࢆᐃ㔞ࡋࠊ⣽⬊⏕Ꮡ⋡ࢆồࡵ࡚࠸ࡿࠋHPLC/UPLCࢆ฼⏝ࡋࡓ࣐࣍ࣝࢨࣥᐃ㔞࣭⣽⬊⏕Ꮡ⋡⟬ฟ࡟ࡘ࠸࡚ࡣࠊCE ࡟ࡼࡾ⓶⭵่⃭ᛶヨ㦂࡟⏝࠸ࡽࢀࡿࣄ
ࢺ⤌⧊ࣔࢹࣝ࡜ྜࢃࡏ࡚ࣂࣜࢹ࣮ࢩࣙࣥࡀ⾜ࢃࢀ࡚࠸ࡿࠋ6㸬ヨ㦂ἲࡢಙ㢗ᛶ
6-1. ᢏ⾡⛣㌿ᛶ ࣂࣜࢹ࣮ࢩࣙࣥヨ㦂ࢆ㛤ጞࡍࡿ๓࡟ࠊࣂࣜࢹ࣮ࢩࣙࣥཧຍ᪋タࡢᢏ⾡⪅㸦᪋タᙜࡓࡾ 3 ྡ㸧࡟ᑐࡋ࡚ᢏ⾡⩦ᚓࡢࡓࡵࡢࢺ࣮ࣞࢽࣥࢢࢆ⾜ࡗࡓࠋࡑࡢᚋ࡛ࠊ8 ≀㉁ࢆ⏝࠸࡚ᢏ⾡⛣㌿ࡢ☜ㄆࢆ⾜ࡗࡓ࡜ࡇࢁࠊ␗࡞ࡿุᐃࡣ 1 ᪋タࡢᢏ⾡⪅ 1 ྡࡢ 1 ᾮయ≀㉁ࡢࡳ࡛࠶ࡗࡓࠋEpiOcularTM EIT ࢆᐇ᪋ࡍࡿヨ㦂᪋タࡢᢏ⾡⩦ᚓࢆ☜࠿ࡵࡿࡓࡵࡢ⇍㐩ᗘ☜ㄆ≀㉁ࡢ୍ぴࡣࠊAppendix 2 ࡟࠶ࡿࠋ713

2016 ᖺ 1 ᭶ 25 ᪥

6-2. ᪋タෆ෌⌧ᛶࣂࣜࢹ࣮ࢩࣙࣥヨ㦂࡛ࡣ᪋タࡈ࡜࡟ 1 ⿕㦂≀㉁࡟ࡘࡁ」ᩘᅇࡢヨ㦂ࢆ⾜ࡗ࡚࠸ࡿࠋᮏヨ㦂࡛ࡣࠊ
GHS ศ㢮ุᐃࡢ᪋タࡈ࡜ࡢ᪋タෆ෌⌧ᛶࡣ 94.2–96.2%࡛࠶ࡗࡓ㸦ᅛయ≀㉁ࡢࢹ࣮ࢱࢆྵࡴ㸧ࠋ1 ᪋タ࡛⾜ࢃࢀࡓ㏣ຍヨ㦂࡛ࡢ᪋タෆ෌⌧ᛶࡣ 96.6%࡛࠶ࡗࡓࠋࡇࢀࡽࡢ್ࡣ EURL ECVAM-CE ࣂࣜࢹ࣮ࢩࣙࣥ㐠Ⴀጤဨ఍ࡀᐃࡵࡓᇶ‽㸦85%௨ୖ㸧ࢆ‶ࡓࡋࡓࠋ
6-3. ᪋タ㛫෌⌧ᛶᮏヨ㦂࡛ᚓࡽࢀࡓ⣽⬊⏕Ꮡ⋡㸦」ᩘᅇヨ㦂㸧ࡢᖹᆒ್ࢆࡶ࡜࡟ GHS ศ㢮ุᐃࢆ᪋タࡈ࡜࡟⾜࠸ࠊࡑࡢ୍⮴ᗘࢆ᳨ウࡋࡓ㸦ᅛయ≀㉁ࡢࢹ࣮ࢱࢆྵࡴ㸧ࠋࡑࡢ⤖ᯝࠊGHS ศ㢮ุᐃࡢ᪋タ㛫෌⌧ᛶࡣ 93.2%
࡛࠶ࡗࡓࠋࡇࡢ್ࡣࣂࣜࢹ࣮ࢩࣙࣥ㐠Ⴀጤဨ఍ࡀᐃࡵࡓᇶ‽㸦80%௨ୖ㸧ࢆ‶ࡓࡋࡓࠋࣉࣟࢺࢥࣝ᭱㐺໬ᚋࡢᅛయ≀㉁࡟ᑐࡋ࡚ࡢ GHS ศ㢮ุᐃࡢ᪋タ㛫෌⌧ᛶࡢࢹ࣮ࢱࡣࠊ㏣ຍヨ㦂ࢆ 1 ᪋タࡢࡳ࡛⾜ࡗࡓࡓࡵᏑᅾࡋ࡞࠸ࠋࣂࣜࢹ࣮ࢩࣙࣥ㐠Ⴀጤဨ఍ࡣࠊ᪋タෆ෌⌧ᛶࡣᮏヨ㦂࣭㏣ຍヨ㦂࡜ࡶ㧗࠸್࡛࠶ࡾࠊࡲࡓࠊྠ᫬࡟ࣂࣜࢹ࣮ࢩࣙࣥࢆ⾜ࡗࡓูࡢ RhCE ἲ࡟࠾࠸࡚᭚㟢᫬㛫ࢆኚ᭦ࡋࡓ㝿࡟ࠊኚ᭦๓
࡜ẚ㍑ࡋ࡚ኚ᭦ᚋ࡛ࡶྠ➼ࡢ㧗࠸᪋タ㛫෌⌧ᛶࡀᚓࡽࢀ࡚࠸ࡿࡇ࡜࠿ࡽࠊࣉࣟࢺࢥࣝ᭱㐺໬ᚋࡢ᪋タ㛫෌⌧ᛶࡢ☜ㄆࡣᚲせ࡞࠸࡜ุ᩿ࡋ࡚࠸ࡿࠋESAC ࡢ➨୕⪅ホ౯࡛ࡣࠊࣉࣟࢺࢥࣝ᭱㐺໬ᚋࡢ᪋タ㛫෌⌧ᛶࡀ࡞࠸Ⅼࡀ኱ࡁ࡞ᨭ㞀࡟࡞ࡿ࡜ࡣ⪃࠼࡚࠸࡞࠸ࠋ7㸬ヨ㦂ἲࡢṇ☜ᛶࣂࣜࢹ࣮ࢩࣙࣥሗ࿌᭩࡛ࡢṇ☜ᛶࡢホ౯࡟ࡣࠊࣂࣜࢹ࣮ࢩࣙࣥヨ㦂࡛⏝࠸ࡽࢀࡓ 115 ≀㉁ࡢ࠺ࡕ≀㉁⮬యࡢⰍࡀ࣐࣍ࣝࢨࣥᐃ㔞࡛ࡢ ODᐃࢆጉࡆࡿ 3 ≀㉁࡜ᙉ࠸㑏ඖᛶ≀㉁ 1 ≀㉁ࢆ㝖ࡃ 111 ≀㉁ࡢ

⤖ᯝࡀ⏝࠸ࡽࢀࡓࠋᡂ❧ࡋࡓ඲ヨ㦂ࡢࢹ࣮ࢱࢆ⏝࠸࡚ồࡵࡓ⤖ᯝࡣ⾲ 1 ࡢ㏻ࡾ࡛࠶ࡿࠋEpiOcularTM
EIT ࡢṇ☜ᛶࡣࣂࣜࢹ࣮ࢩࣙࣥ㐠Ⴀጤဨ఍ࡀᐃࡵࡓཷࡅධࢀᇶ‽ࢆ‶ࡓࡋ࡚࠸ࡿࠋ

⾲ 1. EpiOcularTM EIT ࡢṇ☜ᛶ㸫඲ヨ㦂ࢹ࣮ࢱ≀㉁ᩘ

୍⮴ᗘᗘ(%)

ഇ㝜ᛶ⋡(%)

ഇ㝧ᛶ⋡(%)

ᾮయ

52

81.9

1.7

33.3

ᅛయ

59

78.0

6.5

39.3

ᾮయ࣭ᅛయ

111

79.7

4.3

37.0

௦᭰ἲ࡜ࡋ࡚ࡢ
ཷࡅධࢀᇶ‽

- 75

 10

 40

ESAC ࡢ➨୕⪅ホ౯࡛ࡣࠊ⿕㦂≀㉁ࡈ࡜࡟ุᐃࢆ᭱㧗ࢫࢥ࢔㸦Best-caseࠊᚓࡽࢀࡓヨ㦂ࢹ࣮ࢱࡢ࠺
ࡕ୍ࡘ࡛ࡶື≀ヨ㦂ࡢࢹ࣮ࢱ࡜୍⮴ࡋࡓุᐃࡀ࠶ࢀࡤࡑࢀࢆ᥇⏝㸧࡜᭱పࢫࢥ࢔㸦Worst-caseࠊᚓࡽࢀࡓヨ㦂ࢹ࣮ࢱࡢ࠺ࡕ୍ࡘ࡛ࡶື≀ヨ㦂ࡢࢹ࣮ࢱ࡜୍⮴ࡋ࡞࠿ࡗࡓุᐃࡀ࠶ࢀࡤࡑࢀࢆ᥇⏝㸧ࡢ 2 ࣃࢱ࣮࡛ࣥ☜ᐃࡋࠊࡑࡢ⤖ᯝࢆ⏝࠸࡚ṇ☜ᛶࡢ᳨ウࢆࡋ࡚࠸ࡿࠋࡑࡢ⤖ᯝࡣ⾲ 2 ࡢ㏻ࡾ࡛࠶ࡿࠋ᭱పࢫࢥ
࢔࡛ࡣഇ㝧ᛶ⋡࡟ࡘ࠸࡚ࡣཷࡅධࢀᇶ‽ࢆ‶ࡓࡉ࡞࠿ࡗࡓࡀࠊࡑࢀ௨እࡢṇ☜ᛶࡢᩘ್ࡣࡍ࡭࡚ཷࡅධࢀᇶ‽ࢆ‶ࡓࡋࡓࠋᮏヨ㦂ἲࡢண⢭ᗘࡣ᭱పࢫࢥ࢔࡜᭱㧗ࢫࢥ࢔ࡢ㛫࡟࡞ࡿࡇ࡜ࢆ⪃៖ࡍࡿ࡜ࠊ

814

2016 ᖺ 1 ᭶ 25 ᪥

EpiOcularTM EIT ࡢṇ☜ᛶࡣࣂࣜࢹ࣮ࢩࣙࣥ㐠Ⴀጤဨ఍ࡀᐃࡵࡓཷࡅධࢀᇶ‽ࢆ‶ࡓࡍ࡜➨୕⪅ホ౯ࡣ⤖ㄽࡋࡓࠋ࡞࠾ࠊ➨୕⪅ホ౯࡛ࡣࠊࣂࣜࢹ࣮ࢩ࣏࣮ࣙࣥࣞࢺ࡛㝖እࡉࢀࡓᙉ࠸㑏ඖᛶ≀㉁ࡶ⤌ࡳධࢀࡽࢀ࡚࠸ࡿࠋ
⾲ 2. EpiOcularTM EIT ࡢṇ☜ᛶ㸫≀㉁ࡈ࡜ࡢࢹ࣮ࢱ≀㉁ᩘ

୍⮴ᗘᗘ(%)

ഇ㝜ᛶ⋡(%)

ഇ㝧ᛶ⋡(%)

ᾮయ

53

75.5

7.7

40.7

ᅛయ

59

76.3

6.5

42.9

ᾮయ࣭ᅛయ

112

76.1

7.0

41.1

ᾮయ

53

84.9

0.0

29.6

ᅛయ

59

79.7

6.5

35.7

ᾮయ࣭ᅛయ

112

82.1

3.5

32.7

௦᭰ἲ࡜ࡋ࡚ࡢ
ཷࡅධࢀᇶ‽

- 75

 10

 40

᭱పࢫࢥ࢔

᭱㧗ࢫࢥ࢔ࣂࣜࢹ࣮ࢩࣙࣥ࡟⏝࠸ࡽࢀࡓΰྜ≀ࡢᩘࡣ㝈ࡽࢀ࡚࠸ࡓࠋࣂࣜࢹ࣮ࢩࣙࣥヨ㦂࡜ࡣู࡟ࠊື≀ヨ㦂ࡢࢹ࣮ࢱࡀ࠶ࡿ㎰⸆ฎ᪉㸦97 ฎ᪉ࠊ࠺ࡕ༊ศእࡣ 43 ฎ᪉㸧ࢆ⏝࠸࡚ホ౯ࢆ⾜ࡗࡓሗ࿌࡛ࡣࠊṇ☜ᗘ82%ࠊഇ㝜ᛶ⋡ 9%ࠊഇ㝧ᛶ⋡ 28%࡛࠶ࡗࡓ㸦Kolle et al, 2015㸧ࠋ8㸬ヨ㦂ἲࡢ㐺⏝⠊ᅖTG 492 ࡣࠊヨ㦂ἲࡢᛶ㉁࡜ṇ☜ᛶࡢ☜ಖࢆ⪃៖ࡋ࡚ RhCE ἲࡢ㐺⏝࡟௨ୗࡢไ㝈ࢆタࡅ࡚࠸ࡿࠋ1) ࣂࣜࢹ࣮ࢩࣙࣥヨ㦂࡟࠾࠸࡚⿕㦂≀㉁࡟ྵࡵࡽࢀ࡞࠿ࡗࡓẼయ㸦࢞ࢫ㸧࠾ࡼࡧ࢚࢔ࢰ࣮ࣝࡣ㐺⏝≀㉁࠿ࡽ㝖እࡉࢀࡿࠋ2) GHS ༊ศ 1ࠊ༊ศ 2㸦2A࣭2B㸧≀㉁ࡢ᳨ฟ࡟ࡣ⏝࠸ࡿࡇ࡜ࡣ࡛ࡁ࡞࠸ࠋ
9. ᮏጤဨ఍ࡢ⤖ㄽ
EpiOcularTM EIT ࡣ෌⌧ᛶࡶṇ☜ᛶࡶࣂࣜࢹ࣮ࢩࣙࣥ㐠Ⴀጤဨ఍ࡢᐃࡵࡓᇶ‽ࢆ‶ࡓࡋ࡚࠾ࡾࠊᮏጤဨ఍ࡣࣂࣜࢹ࣮ࢩࣙࣥ㐠Ⴀጤဨ఍ࡢᐃࡵࡓᇶ‽ࡣጇᙜ࡛࠶ࡿ࡜⪃࠼ࡿࠋEpiOcularTM EIT ࡟⏝࠸ࡿ
RhCE ⤌⧊ࡣᕷ㈍ࡉࢀ࡚࠾ࡾࠊ࢔࣓ࣜ࢝ࡢ〇㐀ඖࡼࡾධᡭ࡛ࡁࡿࠋRhCE ⤌⧊௨እࡣࠊ≉Ṧ࡞ᶵᮦࡸヨ⸆ࢆᚲせ࡜ࡏࡎࠊᚲせ࡞ᡭᢏࡶ」㞧࡞ࡶࡢ࡛࡞࠸ࠋධᡭࡋࡓ RhCE ⤌⧊ࡀᶵ⬟ⓗ᮲௳ࡢチᐜ⠊ᅖ࡟࠶ࡾࠊ࠿ࡘᐇ᪋ࡍࡿヨ㦂᪋タࡢᢏ⾡⩦ᚓࡀ࢞࢖ࢻࣛ࢖ࣥࡢ⇍㐩ᗘ☜ㄆ≀㉁࡛☜࠿ࡵࡽࢀ࡚࠸ࢀࡤࠊ
EpiOcularTM EIT ࡣ UN GHS ༊ศእ≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚⏝࠸ࡿࡇ࡜ࡀ࡛ࡁࡿࠋ
EpiOcualrTM EIT ࡣ RhCE ἲࢆ௦⾲ࡍࡿࡶࡢ࡜⪃࠼ࡽࢀࡿࡢ࡛ࠊTG 492 ࡟‽ᣐࡋ࡚ᐇ᪋ࡋࡓሙྜࠊ
RhCE ἲࡣ࣎ࢺ࣒࢔ࢵࣉ᪉ᘧ࡛ UN GHS ༊ศእ≀㉁ࢆ᳨ฟࡍࡿ᪉ἲ࡜ࡋ࡚⏝࠸ࡿࡇ࡜ࡀ࡛ࡁࡿࠊ࡜ᮏ
ጤဨ఍ࡣ⪃࠼ࡿࠋ

915

2016 ᖺ 1 ᭶ 25 ᪥

10. ᩥ⊩
EpiOcularTM EIT SOP, Version 9 (April 6, 2015). EpiOcluarTM EIT for the prediction of acuteoculatr irritation of chemicals. Available at: http:// https://eurl-ecvam.jrc.ec.europa.eu/ (as ofNov. 2015)
ESAC (2014) ESAC Opinion based on the ESAC Scientific Peer Review of the ECVAM Eye
Irritation Validation Study (EIVS) and a related Cosmetics Europe study on HPLC/UPLCphotometry as an alternative endpoint detection system for formazan reaction product.
EURL ECVAM-CE (2014) Prospective validation study of Reconstructed human Tissue-based
test methods for identifying chemical not requiring classification for serious eye damage/eyeirritation ̽ Validation Study Report.
Kaluzhny Y et al (2011) Development of the EpiOcularTM Eye Irritation Test for hazard
identification and labelling of eye irritating chemicals in response to the requirements of the EU
cosmetics directive and REACH legislation. ATLA. 39, 339-64.
Kolle SN et al (2015). The EpiOcular™ Eye Irritation Test is the method of choice for in vitro
eye irritation testing of agrochemical formulations: Correlation analysis of EpiOcular Eye
Irritation Test and BCOP test data according to UN GHS, US EPA and Brazil ANVISA
classification schemes. ATLA. 43, 181-198.
OECD (2012) Test Guideline 437. Bovine Corneal Opacity and Permeability test method foridentifying i) chemicals inducing serious eye damage and ii) chemicals not requiringclassification for eye irritation or serious eye damage.
OECD (2012) Test Guideline 438. Isolated Chicken Eye test method for identifying i) chemicals
inducing serious eye damage and ii) chemicals not requiring classification for eye irritation orserious eye damage.
OECD (2012) Test Guideline 460. Fluorescein Leakage test method for identifying ocularcorrosives and severe irritants.
OECD (2015) Test Guideline 492. Reconstructed human Cornea-like Epithelium (RhCE) test
method for identifying chemicals not requiring classification and labelling for eye irritation orserious eye damage.
OECD (2015) Series on Testing & Assessment 216. Performance standards for the assessment of proposed
similar or modified in vitro Reconstructed human Cornea-like Epithelium (RhCE) test method for eye hazard

1016

2016 ᖺ 1 ᭶ 25 ᪥Appendix 1ࣂࣜࢹ࣮ࢩࣙࣥ࡟⏝࠸ࡽࢀࡓ≀㉁ࡢ࢝ࢸࢦ࣮ࣜࡈ࡜ࡢᩘ

115

඲య║่⃭ᛶ GHS ศ㢮༊ศ 130

༊ศ 2A16

༊ศ 2B14༊ศእ55≀㉁ࡢ≉ᛶ ᾮయ

53

ᅛయ

62

Chemical Class
Ether

25Alcohol

19

Aryl

18

Carboxylic acid ester

16

Carboxylic acid

14Alkoxy13

Aromatic heterocyclic halide

10Aryl halide

10Alkyl halide

9Phenol

9Allyl6

Ammonium salt

6Benzyl6

Aliphatic Amine, tertiary

5Alkane, branched with tertiary carbon

5

Aromatic amine

5Dihydroxyl group

5Guanidine

5Saturated heterocyclic fragment

5Sulfate5ὀ㸧ࣂࣜࢹ࣮ࢩࣙࣥሗ࿌᭩ࢆࡶ࡜࡟సᡂࠋChemical Class ࡣ≀㉁ᩘࡢከ࠸ࡶࡢࢆᢳฟࡋࡓࠋ≀㉁࡟ࡼ
ࡗ࡚ࡣ」ᩘࡢ Chemical Class ࡟ࡲࡓࡀࡗ࡚࠸ࡿሙྜࡶ࠶ࡿࠋ

1117

2016 ᖺ 1 ᭶ 25 ᪥Appendix 2RhCE ἲࡢ⇍㐩ᗘ☜ㄆ≀㉁≀㉁ྡ

CAS ␒ྕᛶ≧GHS ศ㢮

Methylthioglycolate2365-48-2

ᾮయ

༊ศ 1

Tetraethylene glycol diacrylate

17831-71-9

ᾮయ

༊ศ 1

2,5-Dimethyl-2,5-hexanediol

110-03-2

ᅛయ༊ศ 1Sodium oxalate

62-76-0ᅛయ༊ศ 118472-51-0

ᾮయ

༊ศ 2A

1,5-Naphthalenediol

83-56-7

ᅛయ༊ศ 2A

Diethyl toluamide

134-62-3

ᾮయ

༊ศ 2B

2,2-Dimethyl-3-methylenebicyclo[2.2.1]heptane

79-92-5

ᅛయ༊ศ 2B

Dipropyl disulphide629-19-6ᾮయ༊ศእPiperonyl butoxide51-03-6ᾮయ༊ศእ

1-Ethyl-3-methylimidazolium ethylsulphate342573-75-7

ᾮయ

༊ศእ

Polyethylene glycol (PEG-40) hydrogenated castor oil

61788-85-0⢓ᛶ≀༊ศእPotassium tetrafluoroborate

14075-53-7

ᅛయ

༊ศእ

1-(4-Chlorophenyl)-3-(3,4-dichlorophenyl)urea

101-20-2ᅛయ

༊ศእ103597-45-1

ᅛయ

༊ศእ

2,4,11,13-Tetraazatetradecane-diimidamine, N,N’’-bis(4-chlorophenyl)- 3,12diimino-,di-D-glucose (20%, aqueous)

2,2’-Methylene-bis-(6-(2H-benzotriazol-2-yl)-4- (1,1,3,3-tetramethylbutyl)phenol)

1218